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Metabolic Bone Disease of Prematurity Zulf Mughal Consultant in Paediatric Bone Disorders Department of Paediatric Endocriology Royal Manchester Children's.

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Presentation on theme: "Metabolic Bone Disease of Prematurity Zulf Mughal Consultant in Paediatric Bone Disorders Department of Paediatric Endocriology Royal Manchester Children's."— Presentation transcript:

1 Metabolic Bone Disease of Prematurity Zulf Mughal Consultant in Paediatric Bone Disorders Department of Paediatric Endocriology Royal Manchester Children's HospitalManchester M13 0JH Bone Study Day, 28 th September 2012

2 Metabolic Bone Disease of Prematurity  Aetiology  Fractures  Assessment  Prevention  Aetiology  Fractures  Assessment  Prevention

3 Aetiology of Metabolic Bone Disease of Prematurity

4  Preterm birth - bulk of the mineral transfer from mother to baby occurs in last third of pregnancy  Inadequate supply of minerals in diet after birth  Increased loss of minerals from infant’s bones after birth: Stoppage of movements Loss of oestrogen Aetiology of Metabolic Bone Disease of Prematurity

5 Increased risk of MBP <1000 gm birth weight (ELBW) Prolonged TPN (>2 weeks) Medications Corticosteroids Frusemide Inadequate bone-nutrient intake Increased urinary Phosphate wastage Aetiology of Metabolic Bone Disease of Prematurity

6 Metabolic Bone Disease of Prematurity  Humerus of 26 week gestation, preterm infant at birth (A) and 6 weeks later (B)  Marked thinning of the cortex  Osteopaenia Poznanski et al. Radiology 1980

7 Greer FR J Peds 1988 Post-natal Changes in Bone Mineralisation

8 Aetiology of Metabolic Bone Disease of Prematurity  Longitudinal study in 85 preterm infants < 1.5 kg  Measured Speed of Sound (SOS m/s)  Tibial length (measured by knemometry)

9 A longitudinal study of tibial speed of sound and lower limb length in preterm infants Knee heel length (mm) Postnatal age (weeks) Tibial SOS (m/s) Knee heel length (mm) over time r=0.96;p<0.001r=-0.28; p<0.033 r = 0.96; p < 0.001

10 A longitudinal study of tibial speed of sound and lower limb length in preterm infants r=0.96;p<0.001r=-0.28; p<0.033

11 Osteocytes 800µ strains 2000µ strains Remodelling Modelling Material quality Architecture LOAD (muscle) STRAIN Hormones (e.g. oestrogen) Cytokines Calcium Vitamins Growth factors etc Frost (1987) Anat Rec 219: 1-9 Post-natal Immobilisation <100 µ strains Mechanostat Bone Deformation

12 Fractures

13 Fracture Incidence in Low Birth Weight Infants  78 VLBW infants; 23 to 36 week gestation week gestation  Human milk or formula fed  69% had evidence of fracture  Most common sites: Ribs Ribs Radius ± ulna Radius ± ulna Femur Femur Koo WWK et al J Pediar Orthop 9:326, 1989

14

15 Subjects  106 infants identified  72 included in the study  Birth weight range 450 - 990g  Gestation range 22 - 33 weeks  All radiographs reviewed by Dr Neville Wright (n=1762)  20% radiographs reviewed by Dr Sarah Russell (n=558) Denise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi:10.1136/adc.2007.136853

16  5 infants (7%) had Rib #s  NONE had posterior shaft #s  All infants with rib #s died  3 infants had non Rib #s Results 1 Number and Sites of rib fractures Denise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi:10.1136/adc.2007.136853

17 Infants with Rib #s vs those with No #s Mann Whitney U Test: Infants with Rib #s vs those with No #s Highest Alkaline Phosphatase (ALP)p = 0.08 Birth weight p = 0.52 Gestation p = 0.22 Corticosteroids p = 0.07 Frusemide p = 0.03 * Chronic Lung Disease p = 0.36 Chest Drains p = 0.57 Total Parentral Nutrition (TPN) p = 0.08 Results 2 Denise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi:10.1136/adc.2007.136853

18 Summary  Only 7% of ELBW infants had radiologically apparent Rib #s  All infants with Rib #s died  None had posterior Rib #  No temporal relationship between CPR & Rib #s  Infants with Rib #s more likely to be treated with Frusemide. Denise Smurthwaite, Neville Wright, Sarah Russell, Anthony Emmerson & Zulf Mughal. Arch. Dis. Child. Fetal Neonatal Ed., Aug 2008; doi:10.1136/adc.2007.136853

19 Assessment & Prevention

20 Assessment of MBDP  Clinical: Serum Calcium and Phosphate concentrations Serum Alkaline Phosphatase activity Serum PTH Radiographs – when necessary  Research: Biochemical markers of bone turnover Bone densitometry Quantitative ultrasound

21  Energy110 -130 Kcal  Calcium140 -180 mg  Phosphorus 80 - 90 mg  Vitamin D 400 IU Needs met by fortification of mother’s milk or premature infant formula Recommended Intake for Premature Infants (per Kg/day)

22 Severe Secondary Hyperparthyroidism

23 Could a program of daily physical activity with adequate dietary intake improve bone mineralisation in premature infants?

24 Moyer-Mileur et al, J Peds 1995 Distal 1/3 Radius Bone Mineral Change by pDXA

25 Thank You


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